Drug intervention to correct iMK deficiency from RUNX-1^+/− iHPCs. (A) Representative flow cytometric analyses of L1-C and L1 day 13 iMk cultures treated with DMSO or J-IN8 and then stained with antibodies against the Mk surface markers CD42a and CD41. (B) Mean ±1 SEM quantitation of the effect of 0.6 μM of JNK inhibitors (J-IN8 or J-IX) on iMk yield as a percentage of DMSO-treated L1-C control cells (n = 4 experiments per study arm; P values by 1-way analysis of variance [ANOVA]). (C) Quantitation of the effect of 0.1 µM RS on iMk yield, as in panel B (n = 4-6 experiments per study arm; P values by 1-way ANOVA). (D-F) Colony-forming assays performed with sorted L1-C and L1 CD42a⁻ and CD42a⁺ iHPCs treated with DMSO or RS (0.1 μM). (D-F) Sorted cells were seeded in MegaCult medium for Mk colonies (D) or MethoCult medium for erythroid colonies (E) and GM colonies (F). Mean ±1 SEM (n = 4 experiments per study arm; P values by 2-way ANOVA). (G) Quantitation of response of agonist-induced PAC-1 binding in drug-treated L1-C and L1 iMks. After 5 days of culture in the presence of DMSO, RS, or J-IN8, day 13 iMks were collected, stained with Mk surface markers and PAC-1, and stimulated with 0.1 U/mL thrombin. Mean ±1 SEM (n = 3 experiments per study arm; P values by 2-way ANOVA).